Cooperation of Striatin 3 and MAP4K4 promotes growth and tissue invasion.

ABSTRACT: MAP4K4 is associated with increased motility and reduced proliferation in tumor cells, but the regulation of this dichotomous functionality remained elusive. We find that MAP4K4 interacts with striatin 3 and 4 (STRN3/4) and that STRN3 and MAP4K4 exert opposing functions in Hippo signaling and clonal growth. However, depletion of either STRN3 or MAP4K4 in medulloblastoma cells reduces invasion, and loss of both proteins abrogates tumor cell growth in the cerebellar tissue. Mechanistically, STRN3 couples MAP4K4 to the protein phosphatase 2A, which inactivates growth repressing activities of MAP4K4. In parallel, STRN3 enables growth factor-induced PKCθ activation and direct phosphorylation of VASP_S157 by MAP4K4, which both are necessary for efficient cell invasion. VASP_S157

SUBMITTER: Migliavacca J 

PROVIDER: S-EPMC9360036 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature